The purpose of this project is to design and implement a comprehensive research development program that will enable the candidate to pursue a successful career as an independent biomedical investigator in the area of prostate cancer and the underlying molecular mechanisms involved in the disease. This three year project will provide the applicant with critical funding and protected research time to facilitate the establishment of a viable research laboratory. In addition, these funds will play a critical role in allowing the applicant to obtain technical research personnel as well as provide resources necessary for the participation in various research conferences. The long-term objective of the applicant is to obtain additional funding (R01) and establish a viable cancer research laboratory. Prostate cancer is the most common non-cutaneous malignancy in American men and the second leading cause of cancer-related deaths in males in the United States. The state of South Carolina (SC) has one of the highest incidence rates of prostate cancer in the country. In addition, more men die of prostate cancer in SC than any other state in the union. Furthermore, incidence among African-American men in SC, are 63% higher than Whites with mortality rates three times higher. It is thought that morbidity and mortality of prostate cancer is partially due to lack of adequate prognosticators and markers for the early detection of disease. The focus of the proposed study is to identify and functionally characterize a potential tumor suppressor gene (TSG) that is located in the region of chromosome 8 that is highly deleted in prostate cancer. The human beta-defensin-1 (DEFB1) gene, which is located at 8p23.2, has been shown to have cytotoxic activity towards mammalian cells. Therefore, the hypothesis of this grant is that DEFB1 may be one of the TSGs and that loss of DEFB1 expression enhances or promotes tumor formation. To investigate our hypothesis, we have developed the following specific aims: 1) Determine the methylation status of the DEFB1 gene promoter. 2) Determine whether over-expression of DEFB1 can induce or enhance apoptosis in cultured cell lines. 3) Determine the role DEFB1 plays in prostate cancer cell proliferation and transformation potential. It is anticipated that these studies will elucidate a better understanding of the role of DEFB1 in tumorigenesis and may be used as a predictor of clinical outcome for prostate cancer disease.